Outline

Objective: The influence of the endothelin system (ETS) on sympathetically mediated hemodynamic responses in humans is largely unknown. Whether any such influence could be genetically determined has not been studied. We investigated the associations of the GNB3 C825T polymorphism with systemic hemodynamic responses to noradrenaline (NA) in the presence and absence of endothelin-A (ETA)-receptor blockade.

Conclusion: To our knowledge this is the first study to show in man in vivo, that the ETS contributes extensively to vascular and cardiac effects of exogenous NA and that this contribution may vary according to genotype. From our results it could be speculated that in healthy GNB3 825T allele carriers Ã-receptor-mediated NA-effects are coupled to endothelin pathways, whereas in CC homozygous individuals alpha-receptor-mediated responses are linked to the ETS.